Cancer patients, e.g., melanoma patients, can be effectively treated by using adoptive immunotherapy. In one adoptive immunotherapy method, a population of white blood cells comprising T cells that react with the cancer cells is isolated from the patient's tumor, grown to large numbers in vitro, and returned to the patient. The protein on the surface that recognizes the tumor (i.e., primarily provides specificity to the T cell:tumor cell interaction) is the T cell receptor. Naturally occurring T cell receptors comprise two subunits, an α-subunit and a β-subunit, and each is a unique protein produced by recombination event in each T cell's genome.
MART-1, NY-ESO-1, and gp100 are tumor-associated antigens known in the art. For example, MART-1 is described by Clay et al., J. Immunol., 163, 507-513 (1999), and U.S. Patent Application Publication No. 2003/0144482 A1; NY-ESO-1 is described by Zeng et al., Cancer Research, 62, 3630-3635 (2002) (and references therein); and “gp100” is described by Morgan et al., J. Immunol., 171, 3287-3295 (2003) (and references therein) and U.S. Patent Application Publication No. 2003/0144482 A1.
Dudley et al. (Science, 298, 850-854 (2002)) showed that the adoptive transfer of highly-selected tumor-reactive T cells directed against self-derived tumor antigens after nonmyeloablative conditioning of patients with metastatic cancer can cause persistent clonal repopulation of T cells. These T cells can proliferate in vivo, display functional activity, and traffic to tumor sites (Dudley et al. (2000)). Consequently, these T cells can cause the regression of metastatic cancer, as well as initiate autoimmunity-mediated cancer-cell destruction. This reference also disclosed that high doses of IL-2 facilitated immunotherapy.
Unfortunately, however, the generation of cancer-reactive lymphocytes is sometimes challenging, and until now, expensive and labor intensive.
It is also desirable to have a variety of T cells available to provide an array of tools to better treat cancer patients. The challenges and expense of generating these T cells, however, places practical restrictions on the number of types of T cells available for adoptive transfer and immunotherapy of patients in need.
Fortunately, the invention mitigates some of the challenges described above. Uses, features, and advantages of the invention will be apparent from the detailed description provided herein.